Future research trends in the major chemical language of bacteria

Abstract

Microbiology was revolutionized in the 1990's by the discovery that many different bacterial species coordinate their behavior when they form a group. In fact, bacteria are now considered multicellular organisms capable of communicating and changing behavior in relation to their cell-density; since 1994 this has been called quorum sensing. This group behavior ensures survival and propagation of the community in many natural environments. Bacterial intercellular communication is mediated by different chemical signals that are synthesized by bacteria which are then either secreted or diffused in the external environment. Bacteria are then able to detect the type and concentration of the signal resulting in regulation of gene expression and, consequently, a synchronized response by the community. The predominant signalling molecules produced by Gram-negative bacteria are N-acyl derivatives of homoserine lactone (AHLs) which have been shown to be produced by over seventy bacterial species. In this essay we discuss the importance of quorum sensing via AHLs and highlight current and future trends in this important field of research.

Figure 1. Examples of the chemical diversity of bacterial quorum sensing signaling molecules.

On the left panel are the structures of the N-acyl homoserine lactones (AHLs) produced by Gram-negative bacteria. At the top of the panel shown is 3-oxo-HSL, in the middle 3-OH-HSL, and at the bottom un-substituted AHL. The R in all three situations varies from C1 to C15. The AI-2, autoinducer-2, is a furanoysl borate ester form and is produced by both Gram-negative and Gram-positive bacteria. PQS, Pseudomonas quinolone signal, 2-heptyl-3-hydroxy-4(1H)-quinolone is produced by some Gram-bacterial species. DSF, diffusible signal factor, is methyl dodecenoic acid and is produced by several Gram-bacterial species.

Figure 2. Schematic representation of a typical N-acyl homoserine lactone (AHL) dependent quorum sensing (QS) system in Gram-negative bacteria.

The LuxI-type proteins are the main class of enzymes capable of synthesizing AHLs and they use the cellular metabolites S-adenosyl-methionine and acetylated acyl carrier proteins to form AHLs. At high population density, the AHL signal accumulates and, at quorum concentrations, it interacts directly with the LuxR-type protein. This induces a conformational change (usually allowing homo-dimerization) resulting in the alteration of the affinity for specific DNA sequences (known as lux-boxes) at target gene promoters changing gene expression.

Figure 3. Cartoon summary of the current and future research trends in the field of N-acyl homoserine lactone (AHL) dependent quorum sensing in bacteria.